Moistening preparation

ABSTRACT

The present invention relates to preparations alleviating the symptoms caused by drying of the mucous membranes of the body. The preparations contain trimethylglycine as an active agent. The invention also relates to the use of trimethylglycine as an agent alleviating the symptoms of dry mucous membranes in different preparations intended for the body care and hygiene, and to a method of alleviating the symptoms, caused by drying, appearing on the mucous membranes of the body.

FIELD OF INVENTION

The present invention relates to preparations alleviating the symptomscaused by drying of the mucous membranes of the body. The preparationscomprise trimethylglycine as an agent affecting the symptoms of drymucous membranes. The invention also relates to a use oftrimethylglycine as an agent alleviating the symptoms of dry mucousmembranes in different preparations intended for the body care andhygiene, and to a method of alleviating the symptoms, caused by drying,appearing on the mucous membranes.

BACKGROUND OF INVENTION

The drying of mucous membranes is a common trouble in adult population,and the usual "cause" of drying is ageing. Every fourth or fifth adultsuffers, for example, from dry mouth (Tenovuo, J. and Soderling, E.,Suomen Hammaslaakarilehti 17 (1994) 972-979). A dry sensation in themouth is more common in women than in men, which is largely due tohormonal changes: a postmenopausal drop in the oestrogen hormoneconcentration causes the mucous membranes of not only the vagina andfemale genitals but also of the mouth and eyes to dry.

The mucous membranes may also dry as a result of some external cause orsituation: dry, windy weather; dry indoor air particularly in winter; atoo high or too low room temperature; incorrect working position at aterminal; or watching of a TV set positioned too high may dry nasal andoral mucous membranes. Nervousness caused, for example, by a publicperformance; continuous speaking, for example, at a lecture; and a stateof stress in which adrenalin production rises also dry the mouth.

In addition, symptoms caused by the drying of mucous membranes are alsoassociated with many diseases and drugs used in their treatment. Drymouth is particularly common in connection with the use ofpsychopharmaceuticals, and drugs used for the treatment of cardiacdiseases, asthma and high blood pressure. In some rheumatic conditionsand in connection with radiotherapy on the neck and nape, both mouth andeyes may dry. Further, for example, anti-allergy and anti-histaminemedication dry nasal mucous membranes, particularly if nasal sprays areused frequently.

The drying of mucous membranes appears as a tight sensation, smarting,itching, pain, irritation, an uncomfortable sensation, problems inspeaking, swallowing or chewing, a need to drink or to blink or moistenthe eyes, to wash, etc. In addition, wounds, or apthae, appear easily ondry mucous membranes, whereby the mucous membranes easily bleed andbecome inflamed. A reduced amount or complete lack of salivaparticularly in a dry mouth increases dental caries and, irrespective ofthe cause of dry mouth, oral hygiene is of primary importance if theoral mucous membranes are dry.

There are different commercially available products to alleviate thesymptoms of dry mucous membranes: xylitol chewing gums and lozengesalleviating the symptoms of dry mouth and stimulating salivation;artificial saliva preparations moistening mucous membranes; eye dropsand gels and nasal sprays and mist sprays alleviating the symptoms ofdry eyes and nose, respectively; hormonal creams and vaginalsuppositories, preparations containing lactic acid bacteria, moisteningvaginal suppositories, and other such products used for alleviating thesymptoms caused by drying of the vaginal mucous membranes. However,still new products are needed to alleviate and eliminate, preferably fora longer period of time and possibly on a prophylactic basis, thesymptoms of dry mucous membranes, simultaneously avoiding the sideeffects of the currently available products.

An object of the present invention is to provide preparations thatalleviate the symptoms caused by the drying of the mucous membranes ofthe body. Another object of the present invention is to provide a methodof alleviating the symptoms, caused by drying, appearing on the mucousmembranes of the mouth, eyes, nose or genitals.

BRIEF DESCRIPTION OF INVENTION

Surprisingly, it has been found that the symptoms caused by drying ofmucous membranes can be alleviated by a preparation that containstrimethylglycine. Trimethylglycine can thus be contained in differentpreparations intended for preventing and alleviating the symptoms,caused by drying, appearing on the mucous membranes of the body.

The present invention relates to a use of trimethylglycine as an agentalleviating the symptoms and removing any unpleasant sensations causedby dry mucous membranes in preparations intended for the body care andhygiene. The present invention also relates to preparations that containtrimethylglycine as an ingredient alleviating the symptoms caused by drymucous membranes. The present invention also relates to a method ofalleviating the symptoms, caused by drying, appearing on the mucousmembranes of the body by introducing a trimethylgiycine-containingpreparation onto the mucous membranes.

DETAILED DESCRIPTION OF INVENTION

In the present invention, the mucous membranes of the body mean themucous membranes of the natural apertures of the body, such as those ofthe mouth, eyes, nose and female genitals. The symptoms of dry mucousmembranes, in turn, mean irritation, smarting, itching, a tightsensation, an unpleasant sensation, pain and other such sensations onthe mucous membranes. With dry mouth are also associated, for example,problems in speaking, chewing and swallowing, aching of the tongue orsalivary glands, and dental caries.

A trimethylglycine-containing preparation of the present invention canhere be a preparation of oral hygiene, for example a tooth paste,powder, gel, mouthwash or mouth spray, a denture adhesive, an artificialsaliva, a chewing gum, a lozenge or the like. Atrimethylglycine-containing preparation according to the presentinvention can also be a preparation applied to the eye, such as an eyedrop, eyewash, ointment or gel; or a preparation administered to thenose, such as a nasal spray, mist spray or drop. In addition, atrimethylglycine-containing preparation according to the presentinvention can be a preparation administered to the mucous membranes ofthe genitals, such as a vaginal suppository, tablet, capsule or cream,or a cream or moist tissue for intimate hygiene, or some other suchpreparation.

The preferred preparations of the invention include preparations usedfor normal every-day oral hygiene, for example tooth pastes,mouthwashes, gels and oral sprays. These preparations are particularlyadvantageous because they allow alleviation of dry mouth condition ofvarying degrees depending on the situation and the severity of thesymptoms. When the dry mouth condition is not severe, it may suffice tobrush the teeth twice daily with a tooth paste that containstrimethylglycine. When the symptoms are more severe, for example ifsalivation has greatly reduced or stopped altogether, or if temporaryalleviation of the dry mouth symptoms is necessary, an oral spraycontaining trimethylglycine may be a suitable preparation.

The preferred preparations of the invention also include preparationsadministered to the eye, such as eye drops and gels. Trimethylglycine isparticularly suitable for these, since it does not irritate the eye.

The preferred preparations of the invention also include preparationsfor moistening the mucous membranes of the genitals, whereby thesymptoms of dry mucous membranes can be alleviated without a use ofhormones, which some women wish to avoid.

In the present invention, trimethylglycine means a naturally occurringquaternary ammonium compound of the formula ##STR1## which is alsogenerally called betaine, trimethylammonioacetate,1-carboxy-N,N,N-trimethylmethaneaminium, inner salt, and glycinebetaine,as an anhydride or monohydrate. In the pure form, it is a whitecrystalline compound that is readily soluble in water but also in loweralcohols, such as methanol and ethanol. Trimethylglycine tastes sweet,and it is not toxic, so it is well suited, for example, to a tooth pasteor mouthwash. Trimethylglycine does not have any irritating orallergenic effects, which is particularly important in preparations thatare administered to the eye. On the contrary, trimethylglycine has beenfound to reduce the irritating effects of some other agents (see EP531,387).

Trimethylglycine has a bipolar structure, and it contains severalmetabolically reactive methyl groups, which it can donate inenzyme-catalyzed reactions. Most organisms can synthesizetrimethylglycine in small quantities, for example, for the methyl donorfunction, but are not able to produce nor store it in large quantities.

At cell level, trimethylglycine has been observed to protect plantsparticularly under stress conditions. In plants trimethylglycinefunctions as an osmolyte and thereby protects cells from the effects ofosmotic stress. It has been used as an agent improving the preservationcharacteristics of plants, and as an agent improving the drought andchill resistance of growing plants. To enhance growth, trimethylglycinehas also been added to fertilizers. Further, trimethylglycine has beenused as an additive in animal feed and odder. It has also been observedto have pharmacological activity, e.g. it prevents detrimental effectsof coccidiosis in broilers.

The best known organisms producing large quantities of trimethylglycineare plants of the genus Chenopodiaceae, such as sugar beet, and somemicrobes and marine invertebrates. It can be obtained e.g. from sugarbeet by chromatographic methods. Trimethyiglycine is commerciallyavailable both as an anhydride and as a monohydrate from Cultor Oy,Finnsugar Bioproducts.

Synthetic long-chain alkyl ester, sulpho, and aluminium salt derivativesof trimethylglycine, commonly--and somewhat misleadingly--called`betaine derivatives` or `betaines` particularly in cosmetic industry,have long been used as amphoteric surfactants, for example, in toothpastes. As examples are mentioned U.S. Pat. NoS. 4,490,355 and4,654,161, and published European Patent Application 692,246, whichdiscloses an oral composition containing, for example, "a quantity ofbetaine that effectively reduces surface tension," which is defined asalkylbetaine. In the examples of the publication, cocoamidopropylbetaineis used. Trimethylglycine is not useful for the above-mentionedpurposes, since its surfactant properties are completely different andit does not foam.

U.S. Pat. No. 5,156,845 teaches a lozenge that contains trimethylglycinehydrochloride and is intended to stimulate salivation and therebyalleviate the dry mouth symptoms. The publication teaches thattrimethylglycine hydrochloride is used in the lozenge as an acedulant.Since trimethylglycine hydrochloride is strongly acidic, it differs inits properties from the trimethylglycine anhydride and trimethylglycinemonohydrate with a neutral pH that are used in the present invention. Ifa strongly acidic compound were contained in a preparation to be appliedto the mucous membranes, buffering, neutralizing agents should be addedto inhibit irritation.

Trimethylglycine is known to moisten the skin. However, the surprisingproperty of trimethylglycine presented by the present invention, i.e.the property of alleviating the symptoms of dry mucous membranes, hasnot been described earlier. Skin and mucous membrane differ from eachother in respect of anatomy: mucous membrane is thinner and containsplenty of blood vessels, and any agents brought to the mucous membraneare more easily absorbed, whereas the function of skin is to protect thebody from foreign agents, i.e. to prevent them from entering the bloodcirculation.

The preparation of the present invention alleviating the symptoms of drymucous membranes contains 0.1 to 25% by weight, preferably 1 to 10% byweight, particularly 2 to 6% by weight of trimethylglycine as ananhydride or a monohydrate, based on the preparation, in water, a salinesolution, an isotonic buffer solution, a water/ethanol mixture, a pasteor cream base or a powdery carrier or some other such suitable base. Asuitable type of preparation is selected according to the purpose. Thepreparation also contains ingredients and additives commonly used in thepreparation concerned.

When the preparation according to the invention is a preparation of oralhygiene, such as a tooth paste or mouthwash, it can contain, in additionto trimethylglycine, remineralization-enhancing compounds, such asfluorine, calcium and phosphate compounds; abrasive agents, such ascalcium carbonate, silica, calcium hydrogen phosphate or magnesiumhydrogen phosphate; sweeteners, such as xylitol, sorbitol or saccharine;antimicrobial agents, such as chlorhexidine, lysozyme, lactoperoxidase,lactoferrine or antibodies; surfactants, such as sodium lauryl sulphate,sodium N-lauroyl sarcosinate, sodiumdodecylbenzenesulphate,alkylamidobetaine or monoglyceride sulphate; anti-oxidants; moisteningagents, such as glycerine, sorbitol or propylene glycol; emulsifiers,such as polyvinyl alcohol; binding agents/viscosity enhancing agents,such as polyethylene glycol; gelling agents, such as carboxymethylcellulose, hydroxyethyl cellulose or raw gum, such as gum tragacanth;stabilizers; preservatives, such as thiomersal or parabenes; flavouringagents, such as peppermint oil, menthol, anise or eucalyptus; colouringagents, such as titanium dioxide; bleaching agents, such as peroxides;and the like; and alcohol and/or water.

When the preparation according to the invention is one that is to beadministered to the eye or nose, it can contain, in addition totrimethylglycine, emulsifiers, such as Pluronic F 28; moistening agents,such as glycerol; viscosity enhancing agents, such as polyethyleneglycol, sodium chloride, and other such agents; and a pharmaceutical,such as an antibiotic; or essential oils (nasal preparation) and water.

When the preparation according to the invention is one that is to beadministered to the vagina, for example a tablet, it can contain, inaddition to trimethylglycine, for example excipients, such asmethylhydroxypropyl cellulose and lactose.

The preparations according to the invention are formulated usingconventional methods well known to those skilled in the art.Trimethylglycine is well suited for use with other agents, so itsinclusion in a preparation will not cause any problems during themanufacture.

The use of trimethylglycine as defined in the invention in preparationsintended for the body care and hygiene produces in the products aneffect that alleviates the symptoms of dry mucous membranes. Sincetrimethylglycine also alleviates the irritating effects of the agentsoptionally contained in the preparation, for example the irritatingeffects of sodium lauryl sulphate used as a foaming agent in toothpastes, as described in EP 531,387, trimethylglycine-containingpreparations can be considered particularly friendly to mucousmembranes. Trimethylglycine itself has not been found to have anyantimicrobial effect on micro-organisms present on mucous membranes, andit has no effect on healthy mucous membranes. Naturally occurringtrimethylglycine is also a welcome alternative to synthetic ingredientsused in many preparations.

The preparation according to the invention has been observed to have along-lasting moistening effect on mucous membranes. It is possible thattrimethylglycine, as a bipolar compound, adheres to the surface of themucous membranes and remains there for a while, binding water andthereby maintaining a moist sensation.

In the following the invention will be described in greater detail bymeans of examples. The examples are provided only by way ofillustration, and they are not to be understood as limiting the scope ofthe invention in any way.

EXAMPLE 1

Effect of trimethylglycine on dry mouth

A trimethylglycine tooth paste (HT1) and a reference tooth paste (HT2)were prepared. Their compositions are presented in Table 1.

                  TABLE 1                                                         ______________________________________                                        Composition of the tooth pastes                                                               HT1 (%)                                                                              HT2 (%)                                                ______________________________________                                        Trimethylglycine  4.0      0                                                  Sorbitol (70%)    50.0     51.05                                              CMC 7MF           1.0      1.0                                                NaF               0.24     0.24                                               Sodiumbenzoate    0.1      0.1                                                Titanium oxide    0.5      0.5                                                Saccharin         0.3      0.3                                                Trisodiumphosphate                                                                              1.1      1.1                                                Carbobol 980 NF   0.2      0.2                                                Colour 432        1.0      1.0                                                Silica Zeodent 113                                                                              20.00    20.00                                              Sodium lauryl sulphate                                                                          2.0      2.0                                                Water             19.56    22.51                                              Total             100.00   100.00                                             ______________________________________                                    

To assess the effects of trimethylglycine on dry mouth, a cross-overdouble blind test was carried out on ten study subjects who sufferedfrom subjective dry mouth sensations and some of whom had been diagnosedas having the Sjogren syndrome. An analysis of the saliva showed thatthe ten study subjects had very low salivation (≦0.6 mlmin, xerostomiapatients).

The test comprised two 2-week test periods. Each study subject wasexamined before and after each 2-week test period. In the cross-overdouble blind test, half the patients first used the reference toothpaste and then the trimethylglycine tooth paste; the other half did viceversa. All the study subjects thus used each tooth paste for two weeks,and a total of four check-ups were conducted.

At the first check-up the study subjects were given accurateinstructions concerning the study, and any medication used was recorded.Likewise, the colour and condition of the mucous membranes of each studysubject, and the appearance and condition of the tongue were recorded.

For a microbiological sample, the study subjects rinsed their mouths forone minute with 5 ml of a saline solution, of which 2×100 μl wererecovered in TSB-containing tubes (Tryptic Soy Broth, Difco). The tubeswere kept at -20° C. before cultivation. The samples were cultured forStreptococcus mutans bacteria using a Bacto Mitis Salivarius Agar dish(Difco) which contained 1.8 mg/l of bacitracin (Sigma), (3 d, 37° C., 7%CO₂); for lactobacilli using Bacto Rogos Agar dishes (Difco; 3 d, 37°C., anaerobically); for yeasts using Bacto Sabouraud Dextrose Agardishes (Difco; 2 d, 37° C., anaerobically); and for total anaerobes(total aa) using Blood Agar Base dishes (Difco) which contained 5% ofsheep blood. The colony number of the microbes was counted.

After the test period, an inquiry was also conducted on subjective drymouth sensations using a questionnaire, which is presented in Table 2.At the last check-up, the study subjects were requested to compare thetwo tooth pastes they had used.

On visual inspection of the study subjects' oral mucous membranes, nosignificant changes associated with the use of tooth paste were observedin either of the test groups. Further, no significant changes associatedwith the use of tooth paste were observed in the microbiologicalparameters describing the health condition of the mouth.

Instead, the study subjects' subjective sensations after the use of thetrimethylglycine tooth paste and the reference tooth paste were observedto have changed in a statistically significant manner. Table 2 shows thequestionnaire and the changes in the study subjects' subjectivesensations. HT1 is the group that used the trimethylglycine tooth paste,HT2 is the group that used the reference tooth paste, and n is thenumber of study subjects.

                                      TABLE 2                                     __________________________________________________________________________    Questionnaire: How did the use of paste HT1/HT2 affect your sensations of     dry                                                                           mouth?                                                                        __________________________________________________________________________                               Changes in xerostomia patients' subjective                                    sensations                                                                    HT1 (n = 10)      HT2 (n = 10)                     Question 1                                                                    How dry is your mouth or tongue in daytime?                                                              no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              very dry (1)-rather dry (2)-not dry (3)                                                                  4/10        6/10  10/10                            Question 2                                                                    How dry is your mouth or tongue at night?                                                                no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              very dry (1)-rather dry (2)-not dry (3)                                                                  7/10        3/10  10/10                            Question 3                                                                    Does your mouth or tongue hurt or smart a lot?                                                           no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              always (1)-sometimes (2)-never (3)                                                                       9/10        1/10  6/10  4/10                       Question 4                                                                    Are your lips dry or do they smart?                                                                      no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              always (1)-sometimes (2)-never (3)                                                                       9/10        1/10  8/10  2/10                       Question 5                                                                    Do you have to drink often in daytime?                                                                   no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              always (1)-sometimes (2)-never (3)                                                                       7/10        3/10  10/10                            Question 6                                                                    Do you have to drink often at night?                                                                     no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              always (1)-sometimes (2)-never (3)                                                                       8/10        2/10  10/10                            Question 7                                                                    Do you drink at meals?     no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              always (1)-sometimes (2)-never (3)                                                                       10/10             10/10                            Question 8                                                                    Do you wake up at night because of dry mouth?                                                            no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced              always (1)-sometimes (2)-never (3)                                                                       8/10        2/10  10/10                            Question 9                                                                    Swallowing is very difficult (1)-somewhat difficult (2)-easy                                             no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced                                         10/10             10/10                            Question 10                                                                   Chewing is very difficult (1)-somewhat difficult (2)-easy                                                no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced                                         10/10             9/10        1/10                 Question 11                                                                   Speaking is very difficult (1)-somewhat difficult (2)-easy                                               no effect                                                                           increased                                                                           reduced                                                                             no effect                                                                           increased                                                                           reduced                                         9/10        1/10  10/10                            Question 12                                                                   How many times per day did you brush your teeth during the test                                               .sub.----------------------------                                             duration/times                                Question 13                                                                   Would you like to continue using the paste?                                                       o yes                                                                              o no why .sub.--------------------------------       Question 14                                                                   If the paste alleviated symptoms of dry mouth, how long did the effect        last?                            <10 min                                                                             about 1/2 hour                                                                        >1 hour                        Question 15                                                                   Did the taste of the paste appeal to you?                                                         o yes                                                                              o no                                                 Question 16                                                                   Was the construction of the paste appropriate?                                                    o yes                                                                              o no                                                 Question 17                                                                   Suggested improvements with respect to the properties of the paste            .sub.------------------------------                                           .sub.------------------------------------------------------------------       Question 18                                                                   Other comments: .sub.--------.sub.----------------------------------------    --------------------------                                                    .sub.------------------------------------------------------------------       Question 19                                                                   Did you notice any difference between pastes 1 and 2?                                                 .sub.--------------------------------                 .sub.------------------------------------------------------------------       Question 20                                                                   Which paste (1 or 2) did you find more pleasant to use?                                               .sub.--------------------------------                 .sub.------------------------------------------------------------------       __________________________________________________________________________

When the study subjects used the trimethylglycine-containing toothpaste, eight questions indicated a reduction in the symptoms: question1, 60%; question 2, 30%; question 3, 10%; question 4, 10%; question 5,30%; question 6, 20%; question 8, 20%; and question 11, 10%. Question 1(how the paste affected sensations of dry mouth in daytime), thereduction in the symptoms was statistically significant (p=0.0034). Twoother questions (questions 2 and 5) also yielded indicative results(p<0.1).

When the study subjects in the reference group used the reference toothpaste, two questions indicated an increase in the symptoms. On answeringthe question "Does your mouth or tongue hurt or smart a lot?" (question3), 4 study subjects out of 10 (40%) felt that they had more symptoms;and on answering the question "Are your lips dry or do they smart?"(question 4), 2 study subjects out of 10 (20%) felt that the symptomshad increased. One question (question 10) indicated a reduction in thesymptoms: 1 out of 10 (10%) felt that chewing had become easier. Theresults are not, how ever, statistically significant.

When the study subjects were asked which tooth paste they would prefer,8 (80%) considered the trimethylglycine-containing paste more pleasant.They pointed out a variety of reasons: a foaming property (50%, n=5), amoistening effect (30%, n=3), the dry tongue felt better (10%, n=1), thegums felt fresher and moister (20%, n=2), and a good taste (20%, n=2).Two study subjects considered the reference paste to be more pleasant:one of them (10%, n=1) felt that the reference tooth paste tasted milderas compared with the trimethylglycine tooth paste, and the other (10%,n=1) considered the reference tooth paste to foam less and cause lesssmarting.

EXAMPLE 2

Effect of trimethylglycine on healthy oral mucous membranes

To assess the effect of trimethylglycine on healthy oral mucousmembranes, 17 voluntary students of dentistry were divided into twogroups: one group (n=8) used the tooth paste (HT1) of Example 1containing 4% trimethylglycine, and the other group (n=9) used thereference tooth paste (HT2) of Example 1. The test was conducted as adouble blind test. Before the test, all the study subjects used the samecommercially available tooth paste (Pepsodent Super Fluor®) so thattheir starting condition was as identical as possible. Also, the studysubjects were given accurate instructions as to the use of the toothpaste.

The study subjects' oral mucous membranes were checked both before theuse of the test tooth paste and after a 2-week use. At the check-up, allplaque was recovered from half the teeth (from sectors I and IV). Theplaque was weighed (wet weight/mg) and transferred to a TSB-containingtube, which was kept at -20° C. The plaque was cultured for S. mutansand total anaerobes (total aa) in the manner described in Example 1. Thecolony number was counted.

The results obtained in the plaque analysis are shown in Table 3. Thequantity of plaque was determined on the basis of its wet weight(mg/half the mouth) and the number of total anaerobes in the plaque. Theresults are given as mean values (±standard deviation) before a 2-weekperiod of use of the product (A) and after the period (B). In Table 3,HT1 is the test group that used the trimethylglycine tooth paste, andHT2 the group that used the reference tooth paste. MS stands for mutansstreptococci, and n is the number of study subjects.

                  TABLE 3                                                         ______________________________________                                        Quantity of dental plaque and mutans streptococci                                        Group HT1   Group HT2                                                         A      B        A        B                                         ______________________________________                                        Wet weight of plaque                                                                       12.8     15.1     7.1    8.1                                     (mg/half the mouth)                                                                        (±14.4)                                                                             (±13.1)                                                                             (±2.9)                                                                            (±3.9)                               Total aa of plaque                                                                         8.3      8.6      8.2    8.4                                                  (±0.6)                                                                              (±0.4)                                                                              (±0.4)                                                                            (±0.5)                               MS of plaque 4.2      4.7      4.9    4.9                                                  (±2.4)                                                                              (±1.6)                                                                              (±2.3)                                                                            (±2.2)                               Number of study                                                                            8             9                                                  subjects                                                                      Statistical significance.sup.1                                                             ns            ns                                                 ______________________________________                                         .sup.1 Statistical testing was conducted using a paired ttest; p ≧     0.05 = ns (= not significant); p < 0.05 = *; p < 0.01 = **; p < 0.001 =       ***.                                                                     

From the study subjects was also recovered total saliva. Salivation wasstimulated with paraffin for 30 seconds, after which 2 ml of saliva wasrecovered. The salivation rate (time) was recorded. For culturingpurposes, 100 μl of saliva was added to a TSB tube, which was kept at-20° C. The saliva was cultured for mutans streptococci (MS) under thesame culture conditions as the plaque; for lactobacilli (LB) usingRogosa Agar dishes; and for yeasts using Sabouraud Agar dishes, asdescribed in Example 1. The colony number of the microbes was counted.

The results of the saliva microbe analysis are shown in Table 4. Theresults are given as mean values (±standard deviation) before a 2-weekperiod of use of the product (A) and after the period (B). In Table 4,HT1 is the test group that used the trimethylglycine tooth paste, HT2 isthe group that used the reference tooth paste, and n is the number ofstudy subjects. LB stands for lactobacilli, and MS for mutansstreptococci.

                  TABLE 4                                                         ______________________________________                                        Microbe data of saliva                                                                   Group HT1   Group HT2                                                         A      B        A        B                                         ______________________________________                                        LB of saliva 3.0      2.8      2.6    2.4                                                  (±2.6)                                                                              (±2.4)                                                                              (±2.0)                                                                            (±1.9)                               MS of saliva 4.3      4.7      4.7    4.7                                                  (±2.0)                                                                              (±0.9)                                                                              (±1.9)                                                                            (±1.9)                               Yeasts of saliva                                                                           1.7      0.8      2.6    2.4                                                  (±1.8)                                                                              (±1.5)                                                                              (±1.5)                                                                            (±1.8)                               Number of study                                                                            8             9                                                  subjects                                                                      Statistical significance.sup.1                                                             ns            ns                                                 ______________________________________                                         .sup.1 Statistical testing was conducted using a paired ttest; p ≧     0.05 = ns; p < 0.05 = *; p < 0.01 = **; p < 0.001 = ***.                 

The tooth paste groups did not differ from each other with respect tothe LB, MS and yeast concentrations of saliva in a manner that would bestatistically significant, when the groups were compared before the testperiod started (Student's t-test). The quantity of plaque (mg/half themouth), the total aa and MS levels did not differ at that point, either.No statistically significant changes that could have been associatedwith the use of the trimethylglycine tooth paste or the reference toothpaste were observed in any parameter (paired t-test).

In the light of the above results, the use of trimethylglycine in atooth paste does not seem to prevent the growth of mutans streptococcior microbes belonging to the normal oral flora, but above all it doesnot enhance their growth, either. The study subjects found the taste ofthe trimethylglycine tooth paste pleasant, and no unpleasant sensationsappeared.

What is claimed is:
 1. A method of alleviating the symptoms caused bydrying of the mucous membranes of the natural apertures of the bodycomprising topically applying onto the mucous membranes a compositioncontaining trimethylglycine as an anhydride or monohydrate.
 2. A methodof alleviating the symptoms caused by drying of the mucous membranes ofthe natural apertures of the body comprising topically applying onto themucous membranes of the mouth a composition containing trimethylglycineas an anhydride or monohydrate.
 3. The method of claim 2 wherein thecomposition is applied as a tooth paste, tooth gel, mouthwash or spray.4. A method of alleviating the symptoms caused by drying of the mucousmembranes of the natural apertures of the body comprising topicallyapplying onto the mucous membranes of the eye a composition containingtrimethylglycine as an anhydride or monohydrate.
 5. The method of claim4 wherein the composition is applied as an eye drop, eye gel orophthalmic ointment.
 6. A method of alleviating the symptoms caused bydrying of the mucous membranes of the natural apertures of the bodycomprising topically applying onto the mucous membranes of the nose acomposition containing trimethylglycine as an anhydride or monohydrate.7. The method of claim 6 wherein the composition is applied as a realnasal spray, mist spray or drop.
 8. A method of alleviating the symptomscaused by drying of the mucous membranes of the natural apertures of thebody comprising topically applying onto the mucous membranes of thevagina a composition containing trimethylglycine as an anhydride ormonohydrate.
 9. The method of claim 8 wherein the composition is appliedas a vaginal cream or suppository.
 10. The method of claim 1, 2, 4, 6 or8 wherein the composition contains 0.1 to 25% by weighttrimethylglycine, based on the entire composition, together with apharmaceutically acceptable base.
 11. The method of claim 10 wherein thecomposition contains 1 to 10% by weight trimethylglycine, based on theentire composition, together with a pharmaceutically acceptable base.12. The method of claim 11 wherein the composition contains 2 to 6% byweight trimethylglycine, based on the entire composition, together witha pharmaceutically acceptable base.